SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells
- The Institute of Cancer Research, London, United Kingdom
- CIC bioGUNE, Spain
Abstract
SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show that SOX11 confers distinct features to ER-negative DCIS.com breast cancer cells, leading to populations enriched with highly plastic hybrid epithelial/mesenchymal cells, which display invasive features and alterations in metastatic tropism when xenografted into mice. We found that SOX11+DCIS tumour cells metastasize to brain and bone at greater frequency and to lungs at lower frequency compared to cells with lower SOX11 levels. High levels of SOX11 leads to the expression of markers associated with mesenchymal state and embryonic cellular phenotypes. Our results suggest that SOX11 may be a potential biomarker for breast tumours with elevated risk of developing metastases and may require more aggressive therapies.
Data availability
Sequencing data have been deposited in ArrayExpress as accession E-MTAB-9108. All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Breast Cancer Now (Programme Funding to the Breast Cancer Now Toby Robins Research Centre)
- Erik Oliemuller
- Richard Newman
- Siu Man Tsang
- Gareth Muirhead
- Farzana Noor
- Syed Haider
- Beatrice A Howard
Cancer Research UK (CRUK: A21855)
- Shane Foo
Spanish Ministry of Education and Science (SAF2017-84934-R)
- Maria dM Vivanco
Government of the Autonomous Community of the Basque Country, the Department of Industry, Tourism and Trade
- Iskander Aurrekoetxea-Rodríguez
- Maria dM Vivanco
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Kay F Macleod, University of Chicago, United States
Ethics
Animal experimentation: All animal work was carried out under UK Home Office PPL number: PB0FA698C (BAH Project licence holder) and personal licenses following local ethical approval of all protocols from The Institute of Cancer Research Ethics Committee and in accordance with local and national guidelines. All surgery was performed under isoflurane anesthesia with appropriate analgesia, and every effort was made to minimise suffering.
Version history
- Received: April 28, 2020
- Accepted: September 9, 2020
- Accepted Manuscript published: September 10, 2020 (version 1)
- Version of Record published: September 25, 2020 (version 2)
Copyright
© 2020, Oliemuller et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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SOX11 promotes epithelial/mesenchymal hybrid state and alters tropism of invasive breast cancer cells
eLife 9:e58374.
https://doi.org/10.7554/eLife.58374
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